LAUSR

AIMS The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histologic grade in patients with resected early-stage lung adenocarcinoma. METHODS 3,297 patients with stage I to IIA resected lung adenocarcinoma who had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ vs. EGFR-WT) and IASLC histologic grade (G1, G2, and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumor (16% vs. 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histologic grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI: 1.04-1.62, p = 0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4% vs. 71.5%, p < 0.001) but not among G1 and G2 patients. CONCLUSIONS EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histologic grading, especially in G3 tumors. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.